1, Induction og apoptotic cell death in immortalized cancer cells by chemotherapy (in vitro)The fragmentation of DNA,an indicator of apotosis, was analyzed in two different lines of human gastric cancer cells (HSC-39 and MKN-28). The fragmentation of DNA was detected in HSC-39 cells after a 1-h incubation wtih adriamycin and cisplatin. However, in MKN-28 cells, the fragmentation of DNA was not detected after a 6-h incubation with both agents. The results suggest that HSC-39 is more sensitive to adriamycin and to cisplatin.2, Induction of apoptotic cell death by preoperative mild chemotherapy (in vivo)We examined whether 5-fluorouracil (5-FU), administered preoperatively (500mg/body/day for 7 days) to patients with gastric cancer or colorectal cancer could increase the induction of apoptosis of cancer cells. Furthermore, we examined the relation between induction of apoptosis and expression of Ki-67, p53 or c-myc, which are reported to be relevant to apoptosis. Apoptosis of cancer cells increased significantly in 5-FU-treated group in both gastric and colorectal carcinomas. Expression of Ki-67 was inversely correlated with the extent of apoptosis. There were no clear correlation between expression of apoptosis and the expression of p53 or c-myc.3, Clinical effects of mild chemotherapyPreoperative mild chemotherapy with 5-FU (500 mg/dody/day for 3 to 14 days) has been performed in patients with gastric cancer or colorectal cancer and the extent of apoptosis was examined. Effects of apoptosis by preoperative 5-FU chemotherapy on survival and didease free period of patients are now studying. Furthermore, mild chemotherapy with 5-FU and low dose of cisplatin, clearly different from conventional intensive chemotherapy, has been performed in patients with recurrent or unresectable patients with gastric cancer. Results, namely, anti-tumor effects and survival period also now studying.